The proposed investigations are designed to expand and provide a better understanding of the chronopharmacology and chronotherapeutics of specific compounds on the physiological system. Attempts will be made to develop a pharmacological agent which will phase shift behavioral patterns by altering the circadian levels of certain biogenic amines at specific times of the day. The research also proposes to investigate the role of circadian rhythms in aged animals relative to pain sensitivity, brain amines and neuroactive peptide levels. Studies are also designed to examine and determine the time for best therapeutics regimens for new antiinflammatory steroids currently being synthesized in our lab. Another study will investigate the nocturnal differences in asthma pathophysiology and the circadian effects on the optimum time for kinetics and therapy of the bronchodilator theophylline in healthy volunteers and asthmatic patients. It is hoped that results obtained from the proposed studies will contribute to a better understanding of the chronopharmacology and chronotherapeutics of various drugs and thus promote more effective and safer treatment regimens.